6-[(2-Methyl­phen­yl)sulfan­yl]-5-propyl­pyrimidine-2,4(1H,3H)-dione

Nadia G Haress; Hazem A Ghabbour; Ali A El-Emam; C S Chidan Kumar; Hoong-Kun Fun

doi:10.1107/S1600536814013269

. 2014 Jun 14;70(Pt 7):o768–o769. doi: 10.1107/S1600536814013269

6-[(2-Methylphenyl)sulfanyl]-5-propylpyrimidine-2,4(1H,3H)-dione

Nadia G Haress ^a, Hazem A Ghabbour ^a, Ali A El-Emam ^a,^b, C S Chidan Kumar ^c,^‡, Hoong-Kun Fun ^a,^c,^*,^§

PMCID: PMC4120546 PMID: 25161558

Abstract

In the title pyrimidine-2,4-dione derivative, C₁₄H₁₆N₂O₂S, the dihedral angle between the six-membered rings is 77.81 (10)°. The molecule is twisted about the C_p—S (p = pyrimidine) bond, with a C—S—C—N torsion angle of −59.01 (17)°. An intramolecular C—H⋯S hydrogen bond generates an S(5) ring motif. In the crystal, bifurcated acceptor N—H⋯O and C—H⋯O hydrogen bonds generate inversion-related dimers incorporating R ₂ ¹(9) and R ₂ ²(8) loops. These dimers are connected into a chain extending along the a-axis direction by a second pair of inversion-related N—H⋯O hydrogen bonds, forming another R ₂ ²(8) loop. The crystal structure is further stabilized by weak intermolecular C—H⋯π interactions, generating a three-dimensional network.

Related literature

For the pharmacological activity of pyrimidine-2,4-dione derivatives, see: Al-Abdullah et al. (2011 ▶, 2014 ▶); Tanaka et al. (1995 ▶); Hopkins et al. (1996 ▶); Russ et al. (2003 ▶); Al-Deeb et al. (2013 ▶); Nencka et al. (2006 ▶); El-Emam et al. (2004 ▶); El-Brollosy et al. (2009 ▶, 2011 ▶). For related pyrimidine-2,4-dione structures, see: Al-Omary et al. (2014 ▶); Wang et al. (2006 ▶). For reference bond lengths, see: Allen et al. (1987 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). graphic file with name e-70-0o768-scheme1.jpg

Experimental

Crystal data

C₁₄H₁₆N₂O₂S
M _r = 276.36
Monoclinic,
a = 10.3434 (8) Å
b = 5.3355 (3) Å
c = 24.4948 (18) Å
β = 91.171 (3)°
V = 1351.52 (16) Å³
Z = 4
Mo Kα radiation
μ = 0.24 mm⁻¹
T = 293 K
0.42 × 0.11 × 0.06 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.906, T _max = 0.986
32195 measured reflections
4165 independent reflections
2968 reflections with I > 2σ(I)
R _int = 0.088

Refinement

R[F ² > 2σ(F ²)] = 0.063
wR(F ²) = 0.134
S = 1.08
4165 reflections
182 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.56 e Å⁻³
Δρ_min = −0.37 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536814013269/sj5409sup1.cif

e-70-0o768-sup1.cif^{(23.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814013269/sj5409Isup2.hkl

e-70-0o768-Isup2.hkl^{(204.1KB, hkl)}

Click here for additional data file.^{(5.4KB, cml)}

Supporting information file. DOI: 10.1107/S1600536814013269/sj5409Isup3.cml

CCDC reference: 1007120

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

Cg1 and Cg2 are the centroids of C1–C6 and C8–C11/N1/N2 rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C12—H12B⋯S1	0.97	2.75	3.166 (2)	107
N2—H1N2⋯O2ⁱ	0.82 (2)	2.01 (2)	2.829 (2)	171 (2)
N1—H1N1⋯O1ⁱⁱ	0.83 (3)	1.98 (3)	2.805 (2)	173 (2)
C7—H7B⋯O1ⁱⁱ	0.96	2.58	3.289 (3)	131
C2—H2A⋯Cg2ⁱⁱⁱ	0.93	2.91	3.700 (2)	144
C7—H7B⋯Cg1^iv	0.96	2.85	3.632 (3)	140

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) .

Acknowledgments

The financial support of the Deanship of Scientific Research and the Research Center for Female Scientific and Medical Colleges, King Saud University is greatly appreciated. CSCK thanks Universiti Sains Malaysia for a postdoctoral research fellowship.

supplementary crystallographic information

S1. Comment

Pyrimidine-2,4-diones and their related derivatives have long been known for their diverse chemotherapeutic activities (Al-Abdullah et al., 2014, Al-Deeb et al., 2013) including antiviral activity against HIV (Tanaka et al., 1995; Hopkins et al., 1996; El-Emam et al., 2004), and HSV viruses (Russ et al., 2003). In addition, potent anticancer activity was observed for several pyrimidine-2,4-diones (Nencka et al., 2006). In a continuation of our interest in the chemical and pharmacological properties of pyrimidine and uracil derivatives (Al-Abdullah et al., 2011; El-Brollosy et al., 2009), we have synthesized the title compound (I) as a potential chemotherapeutic agent.

In the title compound (Fig. 1), the two six-membered rings (C1–C6 and C8–C11/N1/N2) are essentially planar, with maximum deviations of -0.012 (2) Å at atom C5 and 0.020 (2) Å at atom C10, respectively. The molecule is bent at the S atom with C6–S1–C8–N1 torsion angle of -59.01 (17)°. The heterocycle containing the structural unit CON₂H₂CO forms a dihedral of 77.81 (10)° with the adjacent benzene ring. Bond lengths and angles in (I) show normal values (Allen et al., 1987) and are comparable with those in related structures (Al-Omary et al., 2014; El-Brollosy et al., 2011; Wang et al., 2006). An intramolecular C—H···S hydrogen bond generates an S(5) ring motif. In the crystal structure, bifurcated acceptor N1–H1N1···O1 and C7–H7B···O1 (Table 1) hydrogen bonds link the two adjacent molecules into centrosymmetric inversion related dimers incorparating R₂¹(9) and R₂²(8) loops (Fig. 2, Bernstein et al., 1995). These dimers are connected into a chain extending along a-axis direction via a pair of N2–H1N2···O2 hydrogen bonds (Table 1) resulting in another R₂²(8) loop (Fig. 2, Bernstein et al., 1995). The crystal structure stability is further consolidated by weak intermolecular C–H···π interactions (Table 1) involving the centroids of the six-membered C8–C11/N1/N2 (Cg1) and C1–C6 benzene (Cg2) rings.

S2. Experimental

A mixture of 6-chloro-5-propyluracil (943 mg, 0.005 mol), o-thiocresol (621 mg, 0.005 mol) and potassium hydroxide (281 mg, 0.005 mol), in ethanol (10 ml), was heated under reflux for 3 h. The solvent was then distilled off in vaccuo and the residue was washed with cold water, dried and crystallized from ethanol to yield 940 mg (68%) of the title compound (C₁₄H₁₆N₂O₂S) as colorless needle crystals. M·P.: 210–212 °C.

¹H NMR (DMSO-d₆, 500.13 MHz): δ 0.84 (t, 3H, CH₂CH₃, J = 7.0 Hz), 1.37–1.40 (m, 2H, CH₂CH₃), 2.33 (s, 3H, Ar—CH₃), 2.43 (t, 2H, CH₂CH₂CH₃, J = 7.0 Hz), 6.92–7.02 (m, 3H, Ar—H), 7.26–7.28 (m, 1H, Ar—H), 10.91 (s, 1H, NH), 11.24 (s, 1H, NH). 13 C NMR (DMSO-d₆, 125.76 MHz): δ 13.72 (CH₂CH₃), 22.06 (CH₂CH₃), 20.12 (Ar—CH₃), 28.22 (CH₂CH₂CH₃), 117.44 (Pyrimidine C-5), 125.90, 126.50, 129.88, 130.20, 133.18, 140.56 (Ar—C), 143.02 (Pyrimidine C-6), 150.53 (C=O), 163.23 (C=O).